Owing to their ability to accumulate in the body, fat-soluble vitamins have a higher potential for toxicity than do water-soluble vitamins. Iron-containing vitamins are the most toxic, especially in pediatric acute ingestions.
Nearly 50,000 instances of vitamin toxicity are reported annually to US poison control centers. [1] According to National Health and Nutrition Examination Survey (NHANES) data, in 2003–2006, 33% of the United States population aged 1 year and older took a multivitamin/mineral supplement (MVM) in a given month. Use rates of MVMs were 25%–27% at age 1–3 years and 14%–19% at 14–18 years. After age 18, use rates increased by age so that by age 71 years or older, 48% of women and 43% of men were taking MVMs. [2]
Owing to their ability to accumulate in the body, fat-soluble vitamins have a higher potential for toxicity than do water-soluble vitamins. Iron-containing vitamins are the most toxic, especially in pediatric acute ingestions. (See Prognosis, Workup, Treatment, and Medication.)
Vitamin A
An important fat-soluble vitamin, vitamin A’s basic molecule is a retinol, or vitamin A alcohol. After absorption, retinol is transported via chylomicrons to the liver, where it is either stored as retinol ester or reexported into the plasma in combination with retinol-binding protein for delivery to tissue sites.
Dietary vitamin A is obtained from preformed vitamin A (or retinyl esters), which is found in animal foods (liver, milk, kidney, fish oil), fortified foods, and drug supplements. Dietary vitamin A is also obtained from provitamin A carotenoids from plant sources, principally carrots. Dietary vitamin A is available mainly as preformed vitamin A in western countries and as provitamin A carotenoids in developing countries.
Supplements are typically 10,000-50,000 international units (IU) per capsule. Fish-liver oils may contain more than 180,000 IU/g. The acute toxic dose of vitamin A is 25,000 IU/kg, and the chronic toxic dose is 4000 IU/kg every day for 6-15 months. (Beta-carotene [ie, provitamin A] is converted to retinol but not rapidly enough for acute toxicity.)
IU is not a Joint Commission on Accreditation of Healthcare Organizations [JACHO]–approved abbreviation, and it must be spelled out on patients' charts and in prescriptions.
RDAs
Because the body can make use of both preformed vitamin A and provitamin A carotenoids that it converts into vitamin A (retinol), and these substances have different bioactivity levels, the recommended dietary allowances (RDAs) for vitamin A are given as mcg of retinol activity equivalents (RAE). The RDAs for vitamin A are as follows [3] :
Males (>14 y) - 900 mcg RAE
Females (>14 y) - 700 mcg RAE
Pregnancy (14-18 y) - 750 mcg RAE
Pregnancy (19-50 y) - 770 mcg RAE
Lactation (14-18 y) - 1200 mcg RAE
Lactation (19-50 y) - 1300 mcg RAE
The RDAs for children are as follows:
0-6 months - 400 mcg RAE
7-12 months - 500 mcg RAE
1-3 years - 300 mcg RAE
4-8 years - 400 mcg RAE
9-13 years - 600 mcg RAE
Vitamin B1
Vitamin B-1 (ie, thiamine) is found in organ meats, yeast, eggs, and green, leafy vegetables. Vitamin B-1 supplements usually contain 50-500 mg of vitamin B-1 per tablet. This vitamin is a cofactor for pyruvate dehydrogenase in the Krebs cycle. The RDA is 1.5 mg (0.7 mg for children aged 1-4 y).
Vitamin B2
The RDA for vitamin B2 (riboflavin) is 1.7 mg (0.8 mg for children aged 1-4 y). Supplements usually are 25-100 mg.
Vitamin B3
Vitamin B3 (ie, niacin) is found in green vegetables, yeast (pumpernickel bagels may contain 190 mg of niacin), animal proteins, fish, liver, and legumes. Supplements are usually 20-500 mg per tablet.
Vitamin B3 synthesis requires tryptophan. Niacin is converted to nicotinamide adenine dinucleotide (NAD) or nicotinamide adenine dinucleotide phosphate (NADP). NAD and NADP are coenzymes for dehydrogenase-type reactions. In large doses, niacin decreases synthesis of LDL cholesterol level. The RDA is 20 mg (9 mg for children aged 1-4 y).
Vitamin B6
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Vitamin B6 (ie, pyridoxine) is found in poultry, fish, pork, grains, and legumes. Supplements usually are 5-500 mg per tablet.
Vitamin B6 functions in protein and amino acid metabolism. Pyridoxine is the treatment of choice for isoniazid overdose. It is also used, with varying results, for the following conditions [4] :
Premenstrual syndrome (PMS)
Nausea and vomiting during pregnancy
Improved cognitive function and memory
Prevention of cardiovascular disease and cancer
The RDAs for vitamin B6 are as follows:
Age 19-50 years - 1.3 mg
Age 51 years and older (males) - 1.7 mg
Age 51 years and older (females) - 1.5 mg
Pregnancy (19-50 y) - 1.9 mg
Lactation (19-50 y) - 2 mg
The RDAs for children are as follows:
Age 0-6 months (adequate intake) - 0.1 mg
Age 7-12 months (adequate intake) - 0.3 mg
Age 1-3 years - 0.5 mg
Age 4-8 years - 0.6 mg
Age 9-13 years - 1 mg
Age 14-18 years (males) - 1.3 mg
Age 14-18 years (females) - 1.2 mg
Pregnancy (14-18 years) - 1.9 mg
Lactation (14-18 years) - 2 mg
Vitamin B12
Vitamin B12 (ie, cyanocobalamin), which requires an intrinsic factor for absorption, is found in milk products, eggs, fish, poultry, and meat. Supplements usually contain 25-250 mcg of the vitamin per tablet. Vitamin B12 is a treatment of pernicious anemia and cyanide poisoning.
The RDAs for vitamin B12 are as follows [5] :
Age 0-6 months (adequate intake) - 0.4 mcg
Age 7-12 months (adequate intake) - 0.5 mcg
Age 1-3 years - 0.9 mcg
Age 4-8 years - 1.2 mcg
Age 9-13 years - 1.8 mcg
Age 14 years and older - 2.4 mcg
Pregnancy (14 y and older) - 2.6 mcg
Lactation (14 y and older) - 2.8 mcg
Vitamin C
Vitamin C (ie, ascorbic acid) is found in citrus fruits and vegetables. An antioxidant and reducing agent, its controversial uses include treatment of upper respiratory tract infections and cancer. [6] Supplements are usually 100-2000 mg per capsule.
The RDAs for vitamin C are as follows (it has been found that individuals who smoke need an additional 35 mg/day) [7] :
Pregnancy (19 y or older) - 85 mg
Lactation (19 or older) - 120 mg
The RDAs for vitamin C in children are as follows:
Age 0-6 months (adequate intake) - 40 mg
Age 7-12 months (adequate intake) - 50 mg
Age 1-3 years - 15 mg
Age 4-8 years - 25 mg
Age 9-13 years - 45 mg
Age 14-18 years (males) - 75 mg
Age 14-18 years (females) - 65 mg
Pregnancy (14-18 y) - 80 mg
Lactation (14-18 y) - 115 mg
Vitamin D
Vitamin D (ie, cholecalciferol) is present in most dairy products, egg yolks, liver, and fish. It increases serum calcium levels by facilitating calcium absorption and mobilizing calcium from bone. Supplements usually are 400 IU per tablet. The RDAs for vitamin D are as follows [8] :
Age 0-12 months (adequate intake) - 10 mcg (400 IU)
Age 1-70 years (including lactation and pregnancy) - 15 mcg (600 IU)
Age > 70 years - 20 mcg (800 IU)
Vitamin E
Vitamin E is any of a group of at least 8 related fat-soluble compounds with similar biological antioxidant activity, particularly alpha-tocopherol but also including other isomers of tocopherol and the related compound tocotrienol. Vitamin E is found in vegetable oil, nuts, sunflower, wheat, green leafy vegetables, and fish. It is a fat-soluble vitamin that acts as an antioxidant and free-radical scavenger in lipophilic environments. Bile is required for absorption; 25% of vitamin E is absorbed orally. Storage of the vitamin occurs in adipose tissue, the liver, and muscle.
Vitamin E may block absorption of vitamins A and K. In addition, it decreases low-density lipoprotein (LDL) cholesterol level at doses more than 400 IU/day.
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One milligram of synthetic vitamin E (all-rac-alpha-tocopherol acetate) is equivalent to 1 IU of vitamin E. One milligram of natural vitamin E (RRR–alpha tocopherol) is equivalent to 0.45 IU of vitamin E.
In a 2000 report, the Food and Nutrition Board of the National Academy of Sciences specified the RDA of vitamin E as 15 mg/day and listed the tolerable upper intake level (UL) of any alpha-tocopherol form as 1000 mg/day (1500 IU/day). The UL is the upper level that is likely to pose no risk of adverse health effects to almost all people in the general population.
While in most healthy adults, short-term supplementation with up to 1600 IU of vitamin E appears to be well tolerated and have minimal side effects, the long-term safety is questionable. [9, 10] Data suggest a possible increase in mortality and in the incidence of heart failure with long-term use of vitamin E (400 IU or more), especially in patients with chronic diseases. [9] Therefore, a UL of 1000 mg/day may be too high, especially if only the alpha-tocopherol form of vitamin E is used (vitamin E consists of 8 compounds and supplementing only one form can be detrimental). Supplements usually are 100-1000 IU per capsule.
The RDAs for vitamin E are as follows [11] :
Age 14 years and older - 15 mg
Pregnancy (14 y and older) - 15 mg
Lactation (14 y and older) - 19 mg
The RDAs for children are as follows:
Age 0-6 months (adequate intake) - 4 mg
Age 7-12 months (adequate intake) - 5 mg
Age 1-3 years - 6 mg
Age 4-8 years - 7 mg
Age 9-13 years - 11 mgM
Vitamin K
Vitamin K (ie, phytonadione) is produced by intestinal bacteria (vitamin K-2) and is found in green, leafy vegetables; cow's milk; and soy oil (vitamin K-1). Vitamin K-1 supplements are usually 2.5-10 mg. Phytonadione promotes liver synthesis of factors II, VII, IX, and X.
Measured in terms of adequate intake (as opposed to RDA), the recommendations for daily intake of vitamin K are as follows [12] :
Age 19 years or older (males) - 120 mcg
Age 19 years or older (females) - 90 mcg
Pregnancy and lactation (19-50 y) - 90 mcg
Age 0-6 months - 2 mcg
Age 6-12 months - 2.5 mcg
Age 1-3 years - 30 mcg
Age 4-8 years - 55 mcg
Age 9-13 years - 60 mcg
Age 14-18 years - 75 mcg (including pregnancy and lactation)
Folate
Folate, which is found in oranges and green, leafy vegetables, decreases the risk of neural tube defects and may reduce serum homocysteine levels (which are a coronary artery disease risk factor). It may also have a therapeutic role as an adjuvant therapy for the treatment of methanol toxicity, since it enhances the elimination of formate.
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